Safingol [L(−)-threo-dihydrosphinganine; (2S,3S)-2-amino-1,3-octadecanediol] is a synthetic optical isomer (enantiomer) of the naturally occurring sphingolipid, sphinganine (D(+)-erythro-dihydrosphinganine; (2S,3R)-2-amino-1,3-octadecanediol), and has the structure:

Due to its stereochemistry, safingol has variant metabolism compared to native sphinganine both in vitro and in vivo (Stoffel, W and Bister, K., (1973) “Stereospecificities in the Metabolic Reactions of the four Isomeric Sphinganines (Dihydrosphinganines) in Rat Liver.” Hopper-Seyler's Z. Physiol. Chem. 354:S169-181; Maurer, B. M., et al., (2000) “Synergistic Cytotoxicity in Solid Tumor Cell Lines Between N-(4-hydroxyphenyl)retinamide and Modulators of Ceramide Metabolism.” J. Natl. Cancer Inst. 92:1897-1909; Venkatarman, K. and Futerman, A. H., (2001) “Comparison of the metabolism of L-erythro- and L-threo-sphinganines and ceramides in cultured cells and in subcellular fractions.” Biochim Biophys Acta 1530:219-226.). Safingol has been variously reported to be an inhibitor of sphingosine kinase, and the various enzymes of the class, protein kinase C (PKC), including the atypical PKC subclass, PKCζ (PKCzeta), acting at the regulatory subunit of PKCs (Merrill, A. H., Jr., et al., (1986) “Inhibition of phorbol ester-dependent differentiation of human promyelocytic leukemic (HL-60) cells by sphinganine and other long-chain bases.” J. Biol. Chem. 261:12610-12615; Hannun, Y. A., et al., (1986) “Sphingosine inhibition of protein kinase C activity and of phorbol dibutyrate binding in vitro and in human platelets.” J. Biol. Chem. 261:12604-12609). Laboratory investigations suggest that safingol might be effective in the treatment of a variety of solid and hematopoetic cancers as a single agent, or in combination with other anticancer agents (Adams, L. M. et al., (1993) “Effect of the protein kinase C (PKC) inhibitor SPC-100270 on drug accumulation and cytotoxicity in drug resistant and sensitive tumor cells in vitro.” Proc. Am. Assoc. Cancer Res. 34:410; Adams, L. M., et al., (1993) “Combined effect of the chemopotentiator SPC-100270, a protein kinase C (PKC) inhibitor, and doxorubicin (DOX) or cisplatin (CIS) on murine isografts and human tumor xenografts.” Proc. Am. Assoc. Cancer Res. 34:410; Seimann, D. W., et al. (1993) “Threo-dihydrosphingosine potentiates the in vivo antitumor efficacy of cisplatin and adriamycin.” Proc. Am. Assoc. Cancer Res. 34:411; Schwartz, G. K., et al. (1995) “Potentiation of apoptosis by treatment with the protein kinase C specific inhibitor safingol in mitomycin-C treated gastric cancer cells.” J. Natl. Cancer Inst. 8:1394-1399; Maurer, B. M. et al., (2000), “Synergistic Cytotoxicity in Solid Tumor Cell Lines Between N-(4-hydroxyphenyl)retinamide and Modulators of Ceramide Metabolism” J. Natl. Cancer Inst. 92:1897-1909; Amin, H. M. et al., (2000) “Characterization of apoptosis induced by protein kinase C Inhibitors and its modulation by the caspase pathway in acute promyelocytic leukaemia.” Br. J. Haematol 110:552-562.) A method of inhibiting oxidative burst in neutrophils using safingol as a protein kinase C inhibitors has been described in U.S. Pat. No. 4,816,450 to Bell et al. A certain method of screening to identify chemotherapeutic agents that may have increased anticancer activity when combined with safingol has been described in U.S. Pat. No. 5,821,072 to Schwartz et al. A method of treating cancer consisting of using safingol as a protein kinase C Inhibitor, in combination with other chemotherapeutic agents, has been described in U.S. Pat. No. 6,444,638 to Schwartz, et al. One hindrance to the clinical development of safingol as an anticancer agent, or anticancer potentiating agent, has been its limited aqueous solubility. Safingol can be prepared in lactic acid-containing solution, however, a simple lactic acid solution of safingol causes thrombophlebitis and hemolysis of red cells when given through peripheral veins in animals, although administration via central venous catheter reduced this toxicity (Kedderis, L. B. et al., (1995) “Toxicity of the Protein Kinase C Inhibitor Safingol Administered Alone and in Combination with Chemotherapeutic Agents.” Fund. Appl. Toxicol. 25:201-217). Further, simple lactate acid solutions of safingol are unstable and prone to precipitation. An oil-in-water emulsion formulation of safingol has been described in U.S. Pat. Nos. 5,677,341 and 5,635,536 to Lyons. The emulsion of Lyons suffers from the disadvantage of being high in vegetable oil (5 to 30 g/100 ml). The emulsion formulation of Lyons received an abbreviated Phase I clinical trial in cancer patients, which was terminated prematurely for lack of drug, and is not currently in manufacture. See (Schwartz, G. K., et al., (1997) “A Pilot Clinical/Phamacological Study of the Protein Kinase C-specific Inhibitor Safingol Alone and in Combination with Doxorubicin.” Clin. Cancer Res. 3:537-543. Thus, there is a need for alternative formulations of safingol for intravenous delivery and which might also be used in the treatment of disease states, including cancer.